{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:51:19Z","timestamp":1784242279524,"version":"3.55.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009708","name":"The Novo Nordisk Foundation","doi-asserted-by":"crossref","award":["NNF180C0052045"],"award-info":[{"award-number":["NNF180C0052045"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006304","name":"Aalborg University Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006304","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study included adults (aged 20\u201386) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: \u22120.26 \u00b1 0.64 vs \u22120.17 \u00b1 0.62, <jats:italic>p<\/jats:italic>=0.44; GSRS: \u22120.35 \u00b1 0.62 vs \u22120.32 \u00b1 0.59, <jats:italic>p<\/jats:italic>=0.77; mean \u00b1 SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: \u22120.47 \u00b1 0.78 vs \u22120.33 \u00b1 0.75, <jats:italic>p<\/jats:italic>=0.34; GSRS: \u22120.46 \u00b1 0.90 vs \u22120.35 \u00b1 0.79, <jats:italic>p<\/jats:italic>=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs \u221219 min, <jats:italic>p<\/jats:italic>=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all <jats:italic>p<\/jats:italic>&gt;0.05). The tVNS was well-tolerated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT04143269<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Funding<\/jats:title>\n                <jats:p>The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045)<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-024-06129-0","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T15:02:09Z","timestamp":1711638129000},"page":"1122-1137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-4759","authenticated-orcid":false,"given":"Ditte S.","family":"Kornum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-9053","authenticated-orcid":false,"given":"Davide","family":"Bertoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-0004","authenticated-orcid":false,"given":"Huda","family":"Kufaishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-4843","authenticated-orcid":false,"given":"Anne-Marie","family":"Wegeberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2659-4313","authenticated-orcid":false,"given":"Tina","family":"Okdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-7430","authenticated-orcid":false,"given":"Esben B.","family":"Mark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0101-5219","authenticated-orcid":false,"given":"Katrine L.","family":"H\u00f8yer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-0070","authenticated-orcid":false,"given":"Jens B.","family":"Fr\u00f8kj\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1598-6023","authenticated-orcid":false,"given":"Birgitte","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Krogh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-3476","authenticated-orcid":false,"given":"Christian S.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K.","family":"Knop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-1884","authenticated-orcid":false,"given":"Christina","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-964X","authenticated-orcid":false,"given":"Asbj\u00f8rn M.","family":"Drewes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"issue":"7","key":"6129_CR1","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/dmrr.1223","volume":"27","author":"P Kempler","year":"2011","unstructured":"Kempler P, Amarenco G, Freeman R et al (2011) Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes. 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We also thank the laboratory staff and unblinded personnel at all study sites for their help in conducting this study. Some of the data were presented as an abstract on 31 August 2023 at the Biennial Meeting of the European Society of Neurogastroenterology and Motility, on 17 October 2023 at the 31st United European Gastroenterology Week, and on 30 September 2023 at the 33rd Annual Meeting of the Diabetic Neuropathy Study Group. The graphical abstract was created using Servier Art, licensed under CC BY 4.0. During the course of preparing this work, the authors used Grammarly only to correct spelling and grammatical errors. The authors take full responsibility for all the content of this publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The dataset generated during and analysed in the study is available upon reasonable request from the corresponding author.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open access funding provided by Aalborg University Hospital. The gammaCore devices were provided by electroCore, and the Novo Nordisk Foundation funded the project (grant number NNF180C0052045). The funders were not involved in the design of the study, the collection, analysis and interpretation of data or writing of the report, and did not impose any restrictions regarding publication of the report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"CB had her travelling costs for attending a scientific meeting reimbursed by electroCore. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"AMD, CB, KK, FKK and BB conceptualised and designed the study. All authors contributed to developing the protocol and the logistical planning. AMW and CB handled the randomisation process. DSK, DB, TO and HK were responsible for participant recruitment. DSK, DB, HK, KLH and TO conducted trial days. DSK, TO and EBM performed statistical analyses. DSK drafted the manuscript. All authors reviewed and approved the final version of the manuscript. AMD is the guarantor of this work and accepts full responsibility for the conduct of the study, has access to all data, and controlled the decision to publish.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}